Neural hyperactivity is a core pathophysiological change induced by deletion of an autism risk gene Ash1l in the mouse brain
Gao, Y.; Aljazi, M. B.; He, J.
Show abstract
Autism spectrum disorder (ASD) is a neurodevelopmental disease associated with various gene mutations. Previous genetic and clinical studies report that mutations of the epigenetic gene ASH1L are highly associated with human ASD and intellectual disability (ID). Recent studies demonstrate that loss of Ash1l in the mouse brain is sufficient to induce ASD/ID-like behavioral and cognitive memory deficits, suggesting that disruptive ASH1L mutations are likely to be the causative driver leading to the ASD/ID pathogenesis in human patients. However, the brain pathophysiological changes underlying the Ash1l-deletion-induced ASD/ID-like behavioral and memory deficits remain unknown. Here we show loss of Ash1l in the mouse brain causes locomotor hyperactivity and higher metabolic rates . In addition, the mutant mice display lower thresholds for the convulsant reagent-induced epilepsy and increased neuronal activities in broad brain areas. Thus, our current study reveals that neural hyperactivity is a core pathophysiological change in the Ash1l-deficient mouse brain, which provides a brain-level basis for further studying the cellular and molecular mechanisms underlying the Ash1l-deletion-induced ASD/ID pathogenesis.
Matching journals
The top 8 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Altered auditory maturation in Fragile X syndrome and its involvement in audiogenic seizure susceptibility 93%
- Gait as a Quantitative Translational Outcome Measure inAngelman Syndrome 91%
- Expression changes in immune and epigenetic gene pathways associated with nutritional metabolites in maternal blood from pregnancies resulting in autism and atypical neurodevelopment 90%
Similar papers in this journal
- Arfgef1 haploinsufficiency in mice alters neuronal endosome composition and decreases membrane surface postsynaptic GABAA receptors 94%
- Characterization of mice with cell type-specific Gnal loss of function provides insights on GNAL-linked dystonia 94%
- TDP-43-M323K causes abnormal brain development and progressive cognitive and motor deficits associated with mislocalised and increased levels of TDP-43. 94%
Similar papers in this journal
- Hyperthermia elevates brain temperature and improves behavioural signs in animal models of Autism spectrum disorder. 94%
- Targeting the RHOA pathway improves learning and memory in Kctd13 and 16p11.2 deletion mouse models. 93%
- Neuroanatomy and Behaviour in Mice with a Haploinsufficiency of AT-Rich Interactive Domain 1B (ARID1B) Throughout Development 93%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.